A study investigating an explosive cancer therapy that was developed two years ago by scientists at Rice University has demonstrated its highly promising potential against stubborn drug-resistant cancers in pre-clinical animal trials. The technology, dubbed “quadrapeutics”, marries four clinically approved existing treatments in a lethal combination that is capable of seeking out and destroying cancer cells whilst leaving surrounding non-cancerous tissue unharmed. The study has been published in Nature Medicine.
Some particularly aggressive cancers, such as head and neck or brain cancers, are highly resistant to chemotherapy and radiotherapy and thus are exceedingly difficult to treat, resulting in poor survival rates. Furthermore, if the tumors are interlaced with non-cancerous tissues then surgery may not be able to remove all of the cancerous tissue. Therefore, there has been in a pressing need for the development of novel therapeutics that can amplify existing treatments whilst leaving surrounding healthy tissue unscathed.
In order to achieve this, Rice University combined encapsulated drugs, colloidal gold nanoparticles, short laser pulses and X-rays into a novel system that amplifies the effect of chemotherapy and radiotherapy within cancerous cells.
“Quadrapeutics shifts the therapeutic paradigm for cancer from materials- drugs or nanoparticles- to mechanical events that are triggered on demand only inside cancer cells,” said Dmitri Lapotko, lead author of the study, in a press-release. “Another strategic innovation is in complementing current macrotherapies with microtreatment. We literally bring surgery, chemotherapies and radiation therapies inside cancer cells.”
The therapy involves several different components. First, a clinically proven cancer drug is encapsulated and tagged with antibodies that specifically target cancerous cells. Next, colloidal gold nanoparticles that are also tagged with cancer cell-specific antibodies are injected which then cluster and accumulate inside target cells. These nanoclusters remain dormant until they are activated by either a laser pulse or radiation.
The third phase of the therapy involves the delivery of a near-infrared laser pulse to the tumor which causes a brief evaporation of liquid, resulting in a the transient expansion and breakdown of vapor nanobubbles called “plasmonic nanobubbles”. These nanobubbles both mechanically destruct the cell and magnify the local doses of the chemotherapy drug, meaning that much smaller amounts of cancer drugs can be used. Finally, a low dose of X-ray radiation is aimed at the tumor which is amplified inside the cancer cells by the gold nanoclusters.
“What kills the most-resistant cancer cells is the intracellular synergy of these components and the events we trigger in cells,” said Lapotko in a press-release. “This synergy showed a 100-fold amplification of the therapeutic strength of standard chemoradiation in experiments on cancer cell cultures.”
When the system was tested in mice with aggressive, chemotherapy resistant head and neck squamous cell carcinomas, it was found to be so effective that only between 2-6% of the normal clinical doses of drugs and X-rays were required. Furthermore, the tumors were eliminated within just week one of administering the therapy and the surrounding normal tissues were spared.
Although the study only investigated head and neck tumors, the treatment should be applicable to a variety of different cancers. The researchers are now collaborating with other institutions in order to progress the promising work towards human clinical trials.
Learn more here http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3484.html